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I Jones

Publications and source records attributed to I Jones.

At least 37 records · Page 2Linked to original sources
PubMed2001

Developmental expression patterns of FTZ-F1 homologues in zebrafish (Danio rerio).

The fushi tarazu factor 1 (FTZ-F1) gene family constitutes a subgroup of orphan nuclear receptors which can be divided into two groups (LRH/FTF- and SF-1/Ad4BP-like) based on sequence homology, function, and tissue distribution. Analysis of zebrafish FTZ-F1 homologues (zFF1 and ff1b) during embryogenesis indicated distinct expression patterns for both genes. Besides the previously observed expression in pituitary/hypothalamus and mandibular arch, zFF1 transcripts were also detected in domains corresponding to the pronephric duct, somites, liver, and hindbrain. Additionally, ff1b transcripts were detected at other developmental stages than earlier documented. Comparative sequence analysis showed that zFF1 exhibited higher sequence similarity to the LRH/FTF group than the SF-1/Ad4BP group, whereas ff1b was indistinguishable between the groups. These observations, coupled with obtained expression patterns, indicate that zebrafish FTZ-F1 homologues exhibit characteristics that are indicative of both LRH/FTF- and SF-1/Ad4BP-like genes.

Animals↗
PubMed2001

Molecular genetic approaches to puerperal psychosis.

Puerperal psychosis, an episode of mania or psychosis precipitated by childbirth follows approximately one in 1000 deliveries. The evidence of clinical, outcome and genetic studies supports the hypothesis that the majority of puerperal psychotic episodes are manifestations of an affective disorder diathesis with a puerperal trigger. Furthermore the available evidence supports the hypothesis that genes are involved in susceptibility to both diathesis and trigger. For complex genetic disorders such as affective illness there are marked benefits in focussing on a homogeneous subtype which allows a subset of hypotheses to be tested. Molecular genetic studies of puerperal psychosis provide an excellent example of this strategy, allowing a hierarchy of hypotheses concerning the involvement of neurosteroid pathways in pathophysiology to be tested. Puerperal psychosis results in considerable suffering to a woman and her family. Elucidating the pathophysiological basis of this disorder will lead to better prevention and treatment and, it is anticipated, inform research on affective disorders more generally.

Bipolar Disorder↗
PubMed2001

Developments in the use of baculoviruses for the surface display of complex eukaryotic proteins.

The ability to couple genotype to phenotype has proven to be of immense value in systems such as phage display and has allowed genes encoding novel functions to be selected directly from complex libraries. However, the complexity of many eukaryotic proteins places a severe constraint on successful display in Escherichia coli. This restriction could be resolved if a eukaryotic virus could be similarly engineered for display purposes. Preliminary data have suggested that the baculovirus Autographa californica, a multiple nuclear polyhedrosis virus (AcMNPV) is a candidate for eukaryotic virus display because the insertion of peptides into the native virus coat protein, or the expression of foreign proteins as coat protein fusions, results in incorporation of the sequence of interest onto the surface of virus particles. A variety of strategies are currently under investigation to develop further the display capabilities of AcMNPV and to improve the complexity of library that might be accommodated. Several expression vectors for different forms of surface display have been developed and, coupled with improved recombination strategies, represent progress towards a refined tool for use in functional genomics and in vitro protein evolution.

Animals↗
PubMed2001

Vasoactive intestinal peptide and nitric oxide in the acute phase following burns and trauma.

VIP and NO co-localized in many of the same neurons, are co-released by some of the same physiological stimuli. In this study we seek the divergent roles in relation to tissue injury between the neurotransmitters within 24 h after burn injury. Forty-four subjects were examined. Fourteen were mechanical trauma patients with mean injury severity score (ISS) of 27, 15 burns patients with mean per cent total burn surface area (%TBSA) of 18%, and 15 healthy controls. Patients plasma were withdrawn immediately on admission (OA) and 24 h post-injury (PI). Controls fasted (>10 h) the night before morning sampling. Enzyme-linked immunosorbent assay (ELISA) technique suitable for the measurements of NO and VIP was used. For each comparison between the patients and control groups, NO(2)(-)/NO(3)(-) plasma levels were higher in burn (P<0.001) and trauma (P<0.0005) than controls. VIP was higher in trauma (P<0.05) but not in burns (P=NS). Trauma and human burn injuries are associated with increase levels of NO productions. While VIP rose in trauma, it remained unchanged in burns. The relationship between VIP and NO observed under physiological conditions in thermal and trauma injury may be of importance in wound healing.

Adult↗
PubMed2001

Exclusion of the Darier's disease gene, ATP2A2, as a common susceptibility gene for bipolar disorder.

Bipolar affective disorder is a genetically complex psychiatric disorder with a population prevalence of approximately 1%. We have previously reported cosegregation of bipolar affective disorder and Darier's disease, a dominant skin disorder with a neuropsychiatric component. The gene for Darier's disease was mapped to chromosome 12q23-q24.1 and linkage studies by us and others have subsequently implicated this region as harbouring a susceptibility gene for bipolar affective disorder. In this study we have investigated the Darier's disease gene ATP2A2, the calcium pumping ATPase SERCA2, as a potential susceptibility gene for bipolar disorder under the hypothesis that variations in SERCA2 have pleiotropic effects in brain. Support for this hypothesis comes from clinical evidence of neuropsychiatric abnormalities in Darier's disease, genetic data produced in our study showing non-random clustering of missense mutations in ATP2A2 in neuropsychiatric Darier patients, and functional data demonstrating the role of SERCA2 in intracellular calcium regulation. In a panel of 15 unrelated bipolar patients from multiply affected families showing increased allele sharing at markers in the 12q23-q24.1 region, we performed mutational screening of the ATP2A2 coding sequence, promoter regions, and 3' untranslated region and identified six sequence variations. These were analysed in a large sample of bipolar patients (n = 324) and control subjects (n = 327). Analysis of allele and genotype distributions for all six variations, and of haplotype frequencies showed no evidence for the involvement of ATP2A2 in producing susceptibility to bipolar disorder.

Adult↗
PubMed2001

Safety of a new conjugate meningococcal C vaccine in infants.

BACKGROUND: Group C conjugate meningococcal vaccines (Men C) were introduced into the UK primary immunisation schedule in November 1999. There has been extensive professional and public interest in their efficacy and safety. AIM: To determine the occurrence of at least one uncommon adverse event in infants related to the administration of the Chiron Men C vaccine. METHODS: A total of 2796 infants aged approximately 2 months were recruited into the study from areas in and around Sheffield and from Scotland. They were vaccinated with the Chiron Men C vaccine at 2, 3, and 4 months along with routine immunisations. Data on adverse events occurring one month after each dose were collected actively and prospectively and reviewed for possible relation to the vaccine. RESULTS: There were no deaths. There were no serious adverse events considered definitely or probably caused by the vaccine. Four infants developed serious adverse events (hypotonia, screaming syndrome, maculopapular rash, and agitation, respectively) that were considered possibly related to the vaccine. All recovered completely. Adverse events were seen in 1804 children but were considered possibly related to the vaccine in only 49 (1.8%). On subsequent immunisation there were no recurrences of adverse events considered to be possibly related to the vaccine.

Female↗
PubMed2001

Familiality of the puerperal trigger in bipolar disorder: results of a family study.

OBJECTIVE: Puerperal psychosis, an episode of mania or psychosis precipitated by childbirth, follows approximately one in 1,000 deliveries. The evidence of clinical, outcome, and genetic studies supports the hypothesis that the majority of puerperal psychotic episodes are manifestations of an affective disorder diathesis with a puerperal trigger. Family studies of puerperal psychosis consistently demonstrate familial aggregation of psychiatric (particularly affective) disorder and suggest a major overlap in the familial factors predisposing to puerperal psychosis and bipolar disorder. The single large study that used direct interview of relatives suggested that familial factors play a role in vulnerability to puerperal triggering itself. The authors' goal was to test this hypothesis further. METHOD: They conducted a study of the occurrence of episodes of puerperal psychosis in families multiply affected with bipolar disorder participating in an ongoing molecular genetic study of bipolar disorder in sibling pairs. RESULTS: Episodes of puerperal psychosis followed 81 (26%) of 313 deliveries to 152 parous women with bipolar disorder, 58 (38%) of whom had at least one puerperal psychotic episode. Puerperal episodes clustered in families. Episodes of puerperal psychosis occurred in 74% (N=20) of the 27 parous women with bipolar disorder who had a family history of puerperal psychosis in a first-degree relative but in only 30% (N=38) of the 125 women with bipolar disorder with no such family history. CONCLUSIONS: These results conclusively demonstrate that familial (probably genetic) factors are implicated in susceptibility to triggering of puerperal episodes in women with bipolar disorder. These findings have implications for future research and will be of use clinically in the management of women with bipolar disorder who are considering pregnancy.

Adult↗
PubMed2001

Candidate gene studies of bipolar disorder.

Genetic factors undoubtedly play an important role in determining vulnerability to bipolar disorder but the task of finding susceptibility genes is not trivial. Candidate gene studies, usually employing the association approach, offer the potential to discover the genes of relatively modest effect size that are expected for a complex genetic disorder. Candidate gene approaches depend crucially on our current understanding of disease pathophysiology, and attention has consequently been focussed on a limited range of neurotransmitter systems implicated by the action of drug treatments. Despite no unequivocal, consistently replicated findings, a number of intriguing results have emerged in the literature, both for bipolar disorder in general and for subtypes such as bipolar affective puerperal psychosis and rapid cycling bipolar illness. Genes of particular current interest include those encoding the serotonin transporter, monoamine oxidase A (MAOA) and catechol-O-methyl transferase (COMT). As susceptibility genes are found and knowledge of aetiology advanced it is likely that many more candidate genes in novel biological systems will attract attention.

Bipolar Disorder↗
PubMed2001

Anticholinergic treatment improves glycaemic control in adolescent girls with insulin-dependent diabetes mellitus.

UNLABELLED: Metabolic control often deteriorates during puberty in girls with insulin-dependent diabetes. It is well accepted that there is an abnormality in the growth hormone (GH)-insulin-like growth factor-I (lGF-I) axis in these girls, resulting in reduced IGF-I levels and elevated GH. As GH antagonizes insulin, attempts have previously been made to reduce excess GH secretion through anticholinergic treatment. However, most of these studies have been performed on adult patients. The aim of the present study was to evaluate the effects of 12 wk of oral anticholinergic treatment with Pirenzepine, 100 mg twice daily, in 16 adolescent girls with diabetes. Serum samples of IGF-I, glycated haemoglobin and fasting IGF-binding protein 1 were analysed at initiation and after 3, 8 and 12 wk of Pirenzepine therapy. Nocturnal urinary GH excretion was also examined. Glycated haemoglobin declined significantly after 3 wk of Pirenzepine therapy (9.8 +/- 0.18 vs 9.2 +/- 0.17; p < 0.001) and was still improved at the end of the study. Unexpectedly, nocturnal urinary GH excretion did not change. Serum IGF-I continuously increased during the study, while IGF-binding protein 1 levels were not significantly altered. CONCLUSION: Anticholinergic treatment with Pirenzepine improves glycaemic control in adolescent girls with diabetes. Although nocturnal urinary GH excretion was unchanged there may still be changes in pituitary GH secretion to explain the improvement. Effects of Pirenzepine on gastrointestinal motility can represent other possible mechanisms behind the improved metabolic control.

Adolescent↗
PubMed2001

Molecular genetics of bipolar disorder.

Background A robust body of evidence from family, twin and adoption studies demonstrates the importance of genes in the pathogenesis of bipolar disorder. Recent advances in molecular genetics have made it possible to identify these susceptibility genes. Aims To present an overview for clinical psychiatrists. Method Review of current molecular genetics approaches and emerging findings. Results Occasional families may exist in which a single gene plays a major role in determining susceptibility, but the majority of bipolar disorder involves more complex genetic mechanisms such as the interaction of multiple genes and environmental factors. Molecular genetic positional and candidate gene approaches are being used for the genetic dissection of bipolar disorder. No gene has yet been identified but promising findings are emerging. Regions of interest include chromosomes 4p16, 12q23-q24, 16p13, 21q22, and Xq24-q26. Candidate gene association studies are in progress but no robust positive findings have yet emerged. Conclusion It is almost certain that over the next few years the identification of bipolar susceptiblity genes will have a major impact on our understanding of disease pathophysiology. This is likely to lead to major improvements and treatment in patient care, but will also raise important ethical issues.

Journal Article↗
PubMed2001

Molecular genetics of bipolar disorder.

BACKGROUND: A robust body of evidence from family, twin and adoption studies demonstrates the importance of genes in the pathogenesis of bipolar disorder. Recent advances in molecular genetics have made it possible to identify these susceptibility genes. AIMS: To present an overview for clinical psychiatrists. METHOD: Review of current molecular genetics approaches and emerging findings. RESULTS: Occasional families may exist in which a single gene plays a major role in determining susceptibility, but the majority of bipolar disorder involves more complex genetic mechanisms such as the interaction of multiple genes and environmental factors. Molecular genetic positional and candidate gene approaches are being used for the genetic dissection of bipolar disorder. No gene has yet been identified but promising findings are emerging. Regions of interest include chromosomes 4p16, 12q23-q24, 16p13, 21q22, and Xq24-q26. Candidate gene association studies are in progress but no robust positive findings have yet emerged. CONCLUSION: It is almost certain that over the next few years the identification of bipolar susceptibility genes will have a major impact on our understanding of disease pathophysiology. This is likely to lead to major improvements and treatment in patient care, but will also raise important ethical issues.

Bipolar Disorder↗
PubMed2000

Molecular genetic studies of bipolar disorder and puerperal psychosis at two polymorphisms in the estrogen receptor alpha gene (ESR 1).

A number of lines of evidence point to the possible involvement of estrogen pathways in the pathophysiology of bipolar disorder in general and puerperal psychosis in particular. There is strong evidence from clinical, follow-up, and genetic studies to support the hypothesis that most cases of puerperal psychosis are manifestations of an affective disorder diathesis with a puerperal trigger and that genes influence susceptibility to both diathesis and trigger. The nature of the trigger is unknown but in view of the abrupt onset at a time of major physiological change it is widely believed that biological, probably hormonal, mechanisms are of paramount importance, with estrogen receiving the most attention to date. We have undertaken a case control association study of bipolar disorder and puerperal psychosis at two known polymorphisms within the estrogen receptor alpha gene (ESR 1) in a sample of 219 unrelated bipolar probands and 219 controls. We could exclude these polymorphisms from an important contribution to susceptibility to bipolar disorder with a high level of confidence. We found no support for the hypothesis that they contribute specific susceptibility to the puerperal trigger, but due to the small numbers of puerperal probands (n = 26) no firm conclusions can be drawn regarding their involvement in puerperal psychosis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:850-853, 2000.

Adult↗
PubMed2000

Variation at the serotonin transporter gene influences susceptibility to bipolar affective puerperal psychosis.

Up to half of parous females with bipolar disorder (manic depression) develop an episode of severe psychiatric disturbance, usually called puerperal psychosis, within a few days of giving birth. We report significant evidence (p<0.003) that variation at the serotonin transporter gene exerts a substantial (odds ratio=4) and important (population attributable fraction=69%) influence on susceptibility to such episodes.

Adult↗
PubMed2000

Bipolar disorder and variation at a common polymorphism (A1832G) within exon 8 of the Wolfram gene.

A number of linkage studies provide evidence consistent with the existence of a bipolar susceptibility gene on chromosome 4p16. The gene for Wolfram syndrome, a rare recessive neurodegenerative disorder, lies in this region and has recently been cloned. Psychiatric disturbances including psychosis, mood disorder, and suicide have been reported at increased frequency in Wolfram patients and in heterozygous carriers of a Wolfram mutation. In the current investigation we have undertaken a case-control association study using a single nucleotide polymorphism (causing an amino acid change) in exon 8 of the Wolfram gene in a UK Caucasian sample of 312 Diagnostic and Statistical Manual of Mental Disorders (fourth edition; DSM IV) bipolar I probands and 301 comparison individuals. We found no evidence that variation at this polymorphism influences susceptibility to bipolar disorder. It remains possible that variation at other sites within or near the Wolfram gene plays important roles in determining susceptibility to affective illness. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:154-157, 2000.

Bipolar Disorder↗
PubMed2000

Comparative sequencing and association studies of aromatic L-amino acid decarboxylase in schizophrenia and bipolar disorder.

Aromatic L-amino acid decarboxylase (AADC) is a relatively non specific enzyme involved in the biosynthesis of several classical neurotransmitters including dopamine and 5-hydroxytryptamine (5HT; serotonin). AADC does not catalyse the rate limiting step in either pathway, but is rate limiting in the synthesis of 2-phenylethylamine (2PE) which is a positive modulator of dopaminergic transmission and a candidate natural psychotogenic compound.1 We and others have proposed that polymorphism in AADC resulting in altered 2PE activity might contribute to the pathogenesis of psychosis. In order to test this hypothesis, we have used denaturing high performance liquid chromatography (DHPLC)3 to screen 3943 bases of the AADC gene and its promoter regions for variants that might affect protein structure or expression in 15 unrelated people with schizophrenia, and 15 unrelated people with bipolar disorder. Three polymorphisms were identified by DHPLC: a insertion/deletion polymorphism in the 5' UTR of the neuronal specific mRNA (g.-33-30delAGAG, bases 586-589 of GenBank M77828), a T>A variant in the non-neuronal exon 1 (g. -67T>A, GenBank M88070), and a G>A polymorphism within intron 8 (g. IVS8 +75G>A, GenBank M84598). Case-control analysis did not suggest that genetic polymorphism in the AADC gene is associated with liability for developing schizophrenia or bipolar disorder.

Aromatic-L-Amino-Acid Decarboxylases↗
PubMed2000

An evolutionary approach to psychiatry.

OBJECTIVE: The current mainstream approach to psychiatry, characterised as empirical and phenomenological is questioned here and a new aetiological approach based on evolutionary theory is proposed. METHOD: A brief description of an evolutionary approach to animal behaviour is presented. The psychiatric states of anxiety, depression, 'hysterical' obsession and some aspects of psychosis are compared with related behaviours in other species. RESULTS: It is argued that this approach can be applied to psychiatric behaviour, that behavioural similarities exist between many psychiatric states and normal behaviour in species other than humans and many of these can be understood as adaptive. Some psychiatric states represent abnormally prominent adaptive behaviours, others represent distortions of these behaviours by a pathological process. An important line of thought in current animal behaviour research examines the concepts of self-awareness, consciousness, thought and affect in species other than man. These ideas, from an evolutionary perspective, are extended to psychiatry. A scheme illustrating this process is presented. CONCLUSIONS: We have drawn on relevant behavioural similarities between humans and other animals to show that many psychiatric states are distortions of evolved behaviour. The implications for classification, research and treatment are considerable. In particular this approach may form a bridge between fundamental research in molecular biology and the anthropomorphic approach of psychodynamics.

Adaptation, Psychological↗
PubMed2000

Association analysis of the proneurotensin gene and bipolar disorder.

Neurotensin (NT) localizes within dopaminergic neurones in the mesocortical, mesolimbic and nigrostriatal systems, and it is now clear that NT can selectively modulate dopaminergic neurotransmission. It has therefore been proposed that altered NT function might contribute to the pathogenesis of neuropsychiatric disorders in which disordered dopaminergic neurotransmission is suspected. We have previously screened the gene encoding NT in a sample of schizophrenic and bipolar subjects, and identified three sequence variants. These have now been tested for association with bipolar disorder using a case-control sample of unrelated bipolar subjects and matched controls. No evidence for association was found, and our data therefore suggest that sequence variation in this gene does not make an important contribution to susceptibility to bipolar disorder.

Adult↗